Ocular rosacea is a common tear film and ocular surface disorder causing eye irritation. This disorder is characterized by eye surface inflammation, and a variety of related eye disorders such as blepharitis; meibomian gland disease, including meibomian gland dysfunction and meibomianitis; keratitis; conjunctival hyperemia; and eyelid hyperemia.
A conservative estimate of the number of patients affected with ocular rosacea is 10 million in the United States alone. It has been reported that 15% of patients with ocular rosacea develop recurrent corneal epithelial erosions, a potentially sight-threatening problem. The incidence of ocular rosacea increases with age.
Common complaints of patients suffering from ocular rosacea include blurred or filmy vision, burning or foreign body sensations in the eye, photophobia, and pain severe enough to awaken the person from sleep. Anterior erosion of the mucocutaneous junction of the eyelid is often noted, as well as eyelid and conjunctival infection, eyelid margin irregularity, corneal epithelial changes, and corneal vascularization.
Although patients with ocular rosacea usually have a normal production of aqueous tears by their lacrimal glands, their meibomian glands can atrophy. The meibomian glands are situated upon the inner surface of the eyelids, between the tarsal plates and conjunctiva. The oily secretions of these glands lubricate the eyelids.
Ocular rosacea is characterized by inflammation of the eyelids, referred to as blepharitis. Blepharitis can be categorized anatomically into anterior and posterior blepharitis.
Anterior blepharitis refers to inflammation mainly centered around the eyelashes and follicles. Anterior blepharitis usually is subdivided further into staphylococcal and seborrheic variants. Frequently, a considerable overlap exists in these processes in individual patients.
Posterior blepharitis mainly is related to dysfunction of the meibomian glands. Alterations in secretory metabolism and function lead to disease. The meibomian secretions become more waxlike and begin to block the gland orifices. The stagnant material becomes a growth medium for bacteria and can seep into the deeper eyelid tissue layers, causing inflammation. These processes lead to gland plugging, inspissated material, formation of chalazia and meibomianitis.
Meibomianitis is characterized by inflammation centered about the meibomian glands. The inflammation can lead to meibomian gland dysfunction, which is characterized by the loss of meibomian gland oil from the tear film, an increase in tear film evaporation, a loss of water from the tear film and the development of dry eye surface disease.
Methods of treating ocular rosacea have included treatment of the apparent infection/inflammation of the eyelids or meibomian glands. For example, patients with ocular rosacea have been symptomatically treated with artificial tears, or hot compresses which liquefy the secretions of the meibomian glands. However, these methods provide limited, if any, improvement. Also, patients have been treated with topically applied steroids to the eyelids or ocular surface. However, steroids are not good long-term solutions because of the potential side-effects e.g., cataract and glaucoma.
Additionally, orally administered tetracyclines and tetracycline analogues (e.g., doxycycline and minocycline) having antibiotic activity are commonly and effectively used for prophylactic or therapeutic treatment of meibomian gland disease. However, a disadvantage of using systemically administered antibiotic tetracyclines is that a high percentage of patients are unable to tolerate oral tetracyclines for extended periods of time. Also, patients can build up a resistance to antibiotic tetracyclines.
Recently other methods for treating ocular rosacea have been disclosed. For example, Gilbard discloses topical antibiotic tetracyclines for the treatment of ocular rosacea (International Application WO 00/07601). Additionally, Pflugfelder et al. have disclosed the use of systemic and topical tetracyclines at a sub-antimicrobial dose for the treatment of ocular rosacea (International Application WO 99/58131).
The skin disease acne rosacea often accompanies ocular rosacea. In particular, ocular rosacea is present in approximately 60% of individuals with acne rosacea.
Acne rosacea is characterized by inflammatory lesions and permanent dilation of blood vessels. Acne rosacea can also include papules, pustules, and hypertrophic sebaceous glands in facial flush areas. A manifestation of severe acne rosacea is rhinophyma. Rhinophyma is seen more often in men with acne rosacea than in women. Rhinophyma is characterized by a thickened, lobulated overgrowth of the sebaceous glands and epithelial connective tissue of the nose.
It is well known that acne and ocular rosacea commonly occur together. Nevertheless, no one has disclosed the simultaneous treatment of both disorders.
Since many patients are susceptible to the simultaneous occurrence of both acne rosacea and ocular rosacea, there is a need for a method of simultaneously treating a patient suffering from both types of disorders. It is especially advantageous if a single agent would be effective to treat both types of disorders. The use of a single agent would reduce both the cost and risk of side effects of treatment.